Cancer is the leading cause of death. This disease is currently treated principally by surgical therapy in combination with radiation therapy and/or chemotherapy. Owing to previous advances in medical technology, cancer is now a disease highly curable if early detected, depending on its type. Therefore, there is a demand for a method for detecting a cancer which places neither physical nor economic burdens on cancer patients and can be achieved by convenient tests.
Recently, methods for assaying tumor products such as tumor markers have been widely available. The tumor products refer to, for example, tumor-related antigens, enzymes, particular proteins, metabolites, oncogenes, oncogene products, and tumor suppressor genes. Carcinoembryonic antigen CEA, glycoprotein CA19-9, prostate-specific antigen PSA, calcitonin (peptide hormone produced in the thyroid gland), and the like are exploited as tumor markers in cancer diagnosis for some cancers. For many types of cancers, however, tumor markers useful in cancer diagnosis have not yet been found. In addition, a large majority of currently known tumor markers is present only in very small amounts (of the order of pg/mL) in body fluids and requires highly sensitive assay methods or special techniques for detecting these markers. Under such circumstances, it can be expected that doors will be opened for diagnostic use for various types of cancers if a novel cancer testing approach capable of highly sensitively detecting various types of cancers by convenient operation can be provided.
Meanwhile, in spite of recent development of novel surgical techniques or discovery of novel anticancer agents, the existing cancer treatment has an insufficiently improved outcome. This is because an effective cancer diagnosis technique has not been established for many cancers, except for some cancers. Inability to detect these cancers early is partly responsible for this situation.
With recent advances in molecular biology or cancer immunology, antibodies specifically reacting with cancer, molecular targeting drugs for cancer antigens related to malignant transformation or cancer exacerbation, and the like have been identified, raising expectations on specific cancer therapy targeting cancer antigens.
Among others, a plurality of antibody drugs for cancer treatment targeting antigenic proteins on cancer cells have been launched and used in the cancer treatment. These antibody drugs have received attention because of their certain efficacy as cancer-specific therapeutic agents. A large majority of antigenic proteins targeted by the drugs, however, are also expressed in normal cells. As a result of administering the antibodies, cancer cells as well as normal cells expressing the antigens are therefore damaged, resulting in undesired adverse reactions. In addition, the effects of cancer treatment differ very largely among individuals due to various factors of the individual cancer patients. For example, surgery, chemotherapy, or radiation therapy largely varies in the treatment and prognosis depending on the stages of cancers. Different persons are known to have distinctive sensitivities to the same therapeutic drug for cancers. This indicates that a certain drug is effective for some patients but ineffective for others due to the diversity of individuals.
Thus, as for some therapeutic drugs, their administration to cancer patients is determined by measuring in advance the expression of disease-related genes or proteins in the patients and evaluating whether a particular drug is effective for a patient expressing a particular gene or protein. Specifically, the presence of a cancer antigen in a sample, for example, serum or tissue, derived from a cancer patient is tested in clinical practice by use of a detection method for assaying a disease-related gene or protein of a certain kind of cancer. Then, the administration of a cancer antigen-specific therapeutic drug is determined. For example, cancer tissues from a large bowel cancer patient are evaluated by an immunohistochemical staining EGFR detection method “EGFR pharm (Dako)” to predict the effectiveness of Erbitux® (cetuximab) for the large bowel cancer. Then, the administration of Erbitux is determined. Further, cancer tissues from a breast cancer patient are evaluated by an immunohistochemical staining Her2 detection method “HercepTest” to predict the effectiveness of Herceptin® (trastuzumab) for the breast cancer. Then, the application of Herceptin is determined.
Incidentally, companion animals have been raised recently as family members and often have lifestyles similar to those of their owners. For this reason, from the occurrence of cancers in companion animals, it can reportedly be predicted that their owners have the high risk of developing cancers in the future.
Dogs, typical companion animals, are known to age 7 times more quickly than humans. Reportedly, the number of dogs currently raised is approximately 6.7 million in Japan and approximately 17.64 million in the USA. Rabies shots as well as combined vaccines such as quintuple, septuple, or octuple combination shots are generally available, leading to decreased rates of highly lethal infections including canine parvovirus infection, canine distemper infection, canine parainfluenza virus infection (kennel cough), canine adenovirus type 2 infection (kennel cough), canine infectious hepatitis, canine coronavirus infection, and leptospirosis. An average dog life-span has therefore been increased, and 7-year-old or older dogs account for 35.5% of the total number of pet dogs. The causes of death such as cancer, hypertension, and heart disease are ever increasing in dogs, as in humans. In the USA, approximately 4 million dogs are yearly diagnosed with cancers. Also in Japan, approximately 1.6 million dogs allegedly have some potential tumor. Checkup examination, however, is not very common in companion animals, unlike humans. This leads to the late detection of disease. In most cases, their owners notice pets' symptoms for the first time after tumors have already become large, and then visit animal hospitals. If such large tumors are malignant, even surgical therapy (e.g., surgical operation) or medication using anticancer agents or the like is very often too late to cure the tumors. Tumors confirmed by veterinarians to be malignant are generally treated with anticancer agents without surgery. Even in the case of performing surgery, it is required to secure surgical margins or to take stringent measures for surgery such as measures against the spread of blood or cells during surgery. Desirably, treatment with anticancer agents is initiated immediately after surgery, and a follow-up is also performed at short intervals. Thus, the medication using therapeutic drugs for cancers is also essential for the cancer-affected companion animals. A detection method, if any, for assaying a disease-related gene or protein of a certain kind of cancer permits more effective treatment than ever and is advantageous both for owners and for veterinarians.
Cytoplasmic- and proliferation-associated protein 1 (CAPRIN-1) is an intracellular protein known to be expressed upon activation or cell division of resting normal cells and to form cytoplasmic stress granules with intracellular RNAs to participate in the regulation of transport and translation of mRNAs. Meanwhile, it has been found that: CAPRIN-1 is highly expressed on the membrane surface of breast cancer cells; and an antibody against CAPRIN-1 exerts strong antitumor effects on breast cancer cells (Patent Literature 1). According to another report, the expression of CAPRIN-1 in a patient-derived sample can be measured using an antibody binding to CAPRIN-1 expressed on cell surface to thereby detect a cancer and to evaluate the grade of the cancer (Patent Literature 2). Specifically, the report states that a plasma membrane protein CAPRIN-1 may serve as a target for cancer treatment or the like. As mentioned above, due to the diversity of cancer patients, it is required to test the presence of CAPRIN-1 in a cancer patient-derived sample for determining the administration of a CAPRIN-1-targeting therapeutic drug, for example, an antibody. Nonetheless, there exists no report on a method for detecting CAPRIN-1 for the application of such a specific therapeutic drug, or there exists no reagent for detecting a cancer using a cancer patient-derived sample.